PD-L1 is a cell surface glycoprotein that is one of two known ligands for Programmed Death 1 (PD-1), which is recognized as an important player in immune regulation and the maintenance of peripheral tolerance. Expression of PD-L1 has been observed on the surface of a variety of immune cells, including naive lymphocytes and activated B and T cells, monocytes and dendritic cells (Id.). Furthermore, PD-L1 mRNA is expressed by non-lymphoid tissues including vascular endothelial cells, epithelial cells, muscle cells, and in tonsil and placental tissue. See, e.g., Keir, M. E. et al., Annu Rev Immunol. 26:677-704 (2008); Sharp A. H. et al., Nature Immunol. 8:239-245 (2007); Okazaki T and Honjo T, Internat. immunol. 19:813-824 (2007).
PD-L1 expression has also been observed in a variety of human cancers, and interaction of tumor-cell expressed PD-L1 with PD-1 can induce inhibition or apoptosis of tumor-specific T cells. In large sample sets of e.g. ovarian, renal, colorectal, pancreatic, liver cancers and melanoma it was shown that PD-L1 expression correlated with poor prognosis and reduced overall survival irrespective of subsequent treatment. Anti-PD-1 monoclonal antibodies that block binding of PD-L1 to PD-1 have been shown to have anti-tumor activity against a variety of tumor types, with early human clinical data suggesting that patients whose tumors express PD-L1 are more likely to respond to anti-PD-1 therapy. See, e.g., Iwai et al., PNAS 99:12293-12297 (2002); Ohigashi et al., Clin Cancer Res 11:2947-2953 (2005); Ghebeh et al., Neoplasia 8:190-198 (2006); Hamanishi, J et al., PNAS 104:3360-3365 (2007); Yang et al., Invest Ophthalmol Vis Sci. 49(6):2518-2525 (2008); Gao et al., Clin Cancer Res 15:971-979 (2009); Brahmer J. R. et al., J Clin Oncol. 28:3167-3175 (2010).
A recent report describes the comparison of 15 anti-human PD-L1 antibodies for utility in detecting expression of hPD-L1 in formalin-fixed paraffin-embedded (FFPE) human melanoma samples (Gadiot, J., et al., Cancer 117(10):2192-2201 (2011)). The utility criteria assessed in this comparison were: (1) ability to stain paraffin-embedded tissues, (2) produce low background staining, and (3) blocked binding to PD-L1 by pre-incubation with a PD-L1 fusion protein. The authors concluded that Ab #4059, a rabbit anti-human polyclonal antibody (obtained from ProSci, Poway, Calif. USA), was the only anti-human PD-L1 antibody of the 15 tested to acceptably meet all of these criteria (Id. at 2195, 2nd column).